Yes, your honor, these neurons claim immunity

Your Honor and members of the jury, these neurons on trial, who witnessed the wanton violence and death of their family members and neighbors, are not responsible for the diseases they have been accused of – Parkinson’s disease, Alzheimer’s disease, autism or Multiple Sclerosis. Indeed, they are the victims and claim immunity from prosecution! As in most cases of organized crimes, it’s the fault of both outsiders – the immune system outside the brain – as well as insiders –the immune cells inside the brain (microglia) and the astroglia that ‘stand guard’ at brain capillaries to slow or prevent entry of undesirables into the brain.

To remind the Court, the brain and the body are intimately connected, with each influencing the well-being and/or dysfunction of the other member of the ‘marriage.’ For example, repeated stress, whether it be psychological or physiological in nature, such as infection or surgical trauma, results in peripheral inflammation and movement of monocytes and macrophages (peripheral immune cells) into the brain. This latter event, as I just stated, is made worse due to a partial failure of the astroglia to maintain a ‘tight’ barrier between blood capillaries and the brain (known as the blood brain barrier [BBB]).

Once in ‘forbidden territory,’ that is, the brain, monocytes and macrophages increase the activity of microglia, which can either be good or bad. Let me explain. It’s good if the microglia act like undertakers and remove dying or dead neurons; it’s bad if the microglia become so excited they release chemicals known as cytokines (sigh-toe-kines) that lead to the formation of free radicals, oxidative stress and more dead and dying neurons. Please see my earlier post – ‘Free Radicals – not hippies – and brain diseases of aging. Thus, peripheral inflammation speeds up the neurodegeneration seen in Parkinson’s disease due, in part, to the fact that microglia are sensitized in the aging brain.

As the defense attorney approaches the judge he admits, in a quiet voice, that other parts of the brain have contributed to neuronal loss by inducing peripheral stress and inflammation. Thus, increases in brain cytokines, along with stressors, increase blood levels of corticosterone, a stress hormone which, in turn, further sensitizes brain microglia, leading to increased neuroinflammation – a truly vicious circle.

So, Your Honor and members of the jury, the neurons of the brain that are allegedly responsible for the above described diseases of the brain are truly the victims. Peripheral inflammation, dereliction of duty by the astroglial gatekeepers of the BBB, and frenzied activation of microglia and consequent release of cytokines are the true criminals.

Brain Man

I will be on an extended road trip – no – the Volvo stays home! Look for a new blog in early December.

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